The Politics Behind Parkinson’s Research

Monkeys with symptoms of Parkinson’s disease recreated a dense network of neural pathways (right) after treatment with a type of non-embryonic stem cells. (photo courtesy International Stem Cell Corp.)

Planned Parenthood’s ongoing problem with anti‐abortionists may have an unintended victim: research into Parkinson’s Disease.

Much stem cell research has nothing to do with aborted fetuses. But the lack of clarity and public understanding about the term has meant that research involving all stem cells – embryonic or fetal – is jeopardized. Appropriations are halted. Research gets reduced. Investors walk away.

The irony is that tremendous advances have been made in the research on Parkinson’s using stem cells in the United States and abroad, especially Japan. And the freedom to work with embryonic stem cells could accelerate new discoveries and solutions. No other source of stem cells – such as umbilical cord blood, amniocentesis or adult stem cells –can be as effective in research, experts say.

Over the last decade, stem cell therapy has emerged as a promising strategy to treat Parkinson’s. And much of the research is conducted with cells that are not from embryos. But the perception that the cells are always derived from human embryos has been a major impediment to sustained research, says Dr. D. Eugene Redmond Jr., professor of psychiatry and of neurosurgery at the Yale University School of Medicine. He has used fetal tissue and stem cells in his own research into Parkinson’s. And although the handful of small companies that are working on Parkinson’s with stem cells have been restricted to using a few federally “approved” cell lines in order to obtain retain federal funding, the specter of controversy over abortion continues to affect their research. It also has driven away tens of millions in federal funds and investor capital.

Every time there is a controversy over abortion and the use of stem cells in research, the restrictions on conducting research sets back stem cell research dramatically, notes Congresswoman Diana DeGette (D, Colorado) in her book Sex Science and Stem Cells.

This issue has been entangled in politics for decades. The original Reagan‐ era “moratorium” on funding of research with fetal cadavers was lifted by the Clinton administration in the early 1990’s. Then bipartisan congressional action set strict rules. President George W. Bush’s 2001 executive order restricting research on human embryonic stem cell lines “killed most publicly funded embryonic stem cell research in the United States from that point forward,” notes DeGette. And although in 2009 President Obama lifted many of the restrictions, ethical and moral objections to stem cell and fetal tissue research have continued to plague researchers and restrict or eliminate appropriations.

Demographics is Parkinson’s big enemy. Most patients diagnosed with Parkinson’s are 50 or older, an age group big drug makers may be less likely to target. As many as one million Americans live with Parkinson’s Disease, more than the combined number diagnosed with multiple sclerosis, muscular dystrophy and Lou Gehrig’s disease. And another 50‐ 60,000 new Parkinson’s cases are diagnosed each year. The worldwide picture is much worse. An estimated seven to ten million people suffer from the disease.

Parkinson’s is a common neurodegenerative disease characterized, mainly, by a significant reduction in the number of dopamine neurons in the substantia nigra, a part of the basal ganglia. The National Institutes of Health (NIH) says the brain cells that produce dopamine are destroyed because of Parkinson’s. Without dopamine, motor movement is impossible.

Starting in the early 2000s, International Stem Cell Corporation (ISCO), a Carlsbad, California biotech company, began exploring stem cell therapies for a number of diseases. What the company found was that stem cells looked particularly promising in regenerating the dopamine destroyed by Parkinson’s. But in a politically‐ charged environment, finding the stem cells was extremely problematic. It finally settled on getting its cells from human parthenogenesis –unfertilized eggs. Deriving stem cells in this way does not require destroying an embryo.

But using the parthenogenesis cells, ISCO now has finished conducting animal trials that not only have shown success in restoring cells to produce dopamine but also in restoring normal health to the animals being tested (see illustrations). With a supportive regulatory climate and additional capital, ISCO could significantly accelerate the development process and the time to market for drugs to treat Parkinson’s. Its method does not in any way involve embryos, and might more rapidly move forward if not for its association with the phrase “stem cells.”

In Japan, Shinya Yamanaka, director of the Center for iPS Cell Research and Applications at Kyoto University, has avoided the fetal cell controversy by working with a type of stem cells known as induced pluripotent stem (iPS) cells. These cells are created by inserting certain genes into the DNA of adult cells to reprogram them back to an embryonic‐like state. In 2012 Yamanaka received the Nobel Prize for his work. To treat Parkinson’s, some researchers extract cells from bone marrow (mesenchymal stem cells) and reprogram them.

One of the main advantages of the iPS cells is that they can be obtained from the patient’s own cells, avoiding possible immune rejection. But the risks are that such cells might carry a genetic defect that led to Parkinson’s in the first place. It would also be very difficult and expensive to create and safety‐test that kind of individual cell line for each patient.

Researchers are working around embryonic stem cells with substitutes. But the process is slower, more imperfect and complicated. Greater access to embryonic stem cells could make a world of difference to Parkinson’s sufferers.

The irony about Parkinson’s is that we may be closer to a cure than ever, especially because of recent advances in stem cell research and genomics. But to reach the goal, methods must continue to be explored that are above ethical controversy. That could happen if federal funders were to accelerate funding for Parkinson’s research.

We may be able to find more ways to progress that do not involve embryonic cells. A second way is for more investors to step up. They need to better understand the risks of research and the potential returns from a treatment for Parkinson’s. Perhaps most important is for regulators to accept stem cell research as a mature science with legitimate goals.